Franz-type diffusion cell

F. Netzlaff, K.-H. Kostka, C.-M. Lehr, and U. F. Schaefer. TEWL measurements as a routine method for evaluating the integrity of epidermis sheets in static Franz type diffusion cells in vitro. Limitations shown by transport data testing. Em J. Pharm. Biopharm. 63 44—50 (2006). 

While Franz-type diffusion cells are commonly used to assess in vitro penetration of compounds across the skin, they have also been used for the assessment of compound permeability across the buccal mucosa [19, 71, 104], In this system, buccal mucosa is sandwiched between two chambers, and compound solution is added to the donor chamber with compound-free buffer in the receptor chamber. The receptor chamber is then periodically sampled to assess the amount of compound that has permeated the tissue over time. 

Franz-type diffusion cells (Glass-blowing Service, University of Queensland, Australia). 

Skin permeability is best measured on excised human skin. Skin can be heat-separated epidermis, dermatomed to a particular thickness (typically 200-500 pm) or whole skin with subcutaneous fat removed. The following protocol outlines a standard skin permeability experiment using human epidermis in static Franz-type diffusion cells ... 

Insert magnetic flea in receptor chamber and mount epidermal membranes stratum corneum side up in horizontal Franz-type diffusion cells, that are then placed on a magnetic stirrer plate in a water bath (Fig. 1) (see Note 8). 

Fig. 1. Franz-type diffusion cell for assessment of skin permeation...

In the in vitro human skin model, human skin is obtained (typically from the abdomen or chest), frozen at -30 C and sectioned to split thickness, fnll thickness, or isolated stratum comeum [82], The Franz-type diffusion cell, which consists of donor and receptor chambers separated by skin, is the most widely used device to measure both permeability and penetration. A jacket maintains temperature and contents collected in the receptor chamber are analyzed periodically. 

Figure 14.8 Basic diffusion cell designs. Static horizontal cells may be jacketed [as in the Franz-type) or unjacketed [and temperature controlled using water bath or heating block). Flow-through cells usually have a small receptor chamber to maximize mixing. Side-by-side cells are used mainly for solution vehicles.

Most studies today are conducted in one-chamber diffusion cells that hold receptor fluid beneath the skin. The top surface of the skin is exposed to the environment and is surroimded by a short wall. A tube extends upward from the receptor fluid for manual sample removal. The Franz cell is the most widely known cell of this type (Franz, 1975). A flow-through diffusion cell (Figure 2.1) is a modification of this design that should have a much smaller receptor fluid chamber to permit easy removal of contents with a moderate flow (1 to 2 ml/h) of receptor fluid (Bronaugh and Stewart, 1985). The continual replacement of the receptor fluid pomits maintenance of skin viability when a physiological buffer is used (Collier etal., 1989). This diffusion cell also has the advantage of automatic samphng with the use of a fraction collector. 

Determination of the effects of changes in blood flow through the various regions of the cutaneous microvasculature is obviously not possible using traditional Franz-type isolated membrane diffusion cell studies. The ultimate goal of experimental systems is usually to allow quantitative prediction of the absorption and distribution of topically applied solutes that wfll be applicable to the in vivo situation. Therefore, we can deduce that studies examining the effects of changes in cutaneous blood flow are limited to experimental models in which the microvasculature has been preserved and can be effectively perfused and manipulated. Models reported in the htraature to date include isolated perfused tissue models, anesthetized animal studies, and more recently human and animal cutaneous microdialysis studies. 

In summary, skin penetration tests consist of placing the piece of skin in a diffusion chamber (e.g., Franz-cell-type static diffusion chamber or flow-through diffusion cell) with two compartments. The external side of the skin is turned toward the upper compartment in which the test solution is applied. After a defined contact time with the skin surface, the effect of the surfactant on skin permeability properties is determined, often by means of a penetration marker (e.g., tritiated water). Many variations in penetration studies have been described and the reader is referred to other articles for more details [34,35]. 

Chilcott et al. reported the in vitro measurements of S-labelled SM penetration through human skin (heat-separated epidermal membranes and full thickness skin) using Franz type static diffusion cells at 30-32 °C. The measurements were made after exposing the skin surface to pure SM liquid (finite, 10 pi, and infinite, 20 pi, doses) under occluded and unoccluded conditions and after exposure to saturated SM vapour. 

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